A bio-inductive collagen scaffold that supports human primary tendon-derived cell growth for rotator cuff repair.
Rotator Cuff (RC) tendon tearing is a common clinical problem and there is a high incidence of revision surgery due to re-tearing. In an effort to improve patient outcome and reduce surgical revision, scaffolds have been widely used for augmentation of RC repairs. However, little is known about how scaffolds support tendon stem cell growth or facilitate tendon regeneration. The purpose of this study is to evaluate the structural and biological properties of a bioactive collagen scaffold (BCS) with the potential to promote tendon repair. Additionally, we conducted a pilot clinical study to assess the safety and feasibility of using the BCS for repair of RC tears. A series of physical, ultrastructural, molecular and tests determined the biocompatibility and teno-inductive properties of this BCS. In addition, a prospective case study of 18 patients with RC tendon tears (>20 mm in diameter) was performed in an open-label, single-arm study, involving either mini-open or arthroscopic surgical RC repair with the BCS. Clinical assessment of RC repair status was undertaken by MRI-imaging at baseline, 6 and 12 months and patient evaluated questionnaires were taken at baseline as well as 3, 6 & 12 months. The BCS consists of highly purified type-I collagen, in bundles of varying diameter, arranged in a higher order tri-laminar structure. BCS have minimal immunogenicity, being cell and essentially DNA-free as well as uniformly negative for the porcine α-Gal protein. BCS seeded with human primary tendon-derived cells and exposed to 6% uniaxial loading conditions , supported increased levels of growth and proliferation as well as up-regulating expression of tenocyte differentiation marker genes including TNMD, Ten-C, Mohawk and Collagen-1α1. To test the safety and feasibility of using the BCS for augmentation of RC repairs, we followed the IDEAL framework and conducted a first, open-label single arm prospective case series study of 18 patients. One patient was withdrawn from the study at 3 months due to wound infection unrelated to the BCS. The remaining 17 cases showed that the BCS is safe to be implanted. The patients reported encouraging improvements in functional outcomes (ASES, OSS and Constant-Murley scores), as well as quality of life assessments (AQoL) and a reduction in VAS pain scores. MRI assessment at 12 months revealed complete healing in 64.8% patients (11/17), 3 partial thickness re-tears (17.6%) and 3 full thickness re-tears (17.6%). The BCS is composed of type-I collagen that is free of immunogenic proteins and supports tendon-derived cell growth under mechanical loading . This pilot study shows that it is safe and feasible to use BCS for RC argumentation and further controlled prospective studies are required to demonstrate its efficacy. The results of this study indicate that this bioactive collagen scaffold has unique properties for supporting tendon growth and that it is non-immunogenic. The clinical study further confirms that the scaffold is a promising biological device for augment of human rotator cuff repairs.